Compaction,Compression and consolidation

Views:
 
Category: Education
     
 

Presentation Description

In tablet manufacturing

Comments

Presentation Transcript

PowerPoint Presentation:

1 “COMPACTION,COMPRESSION & CONSOLIDATION IN PREFORMULATION” PREPARED BY: Gosai Madhuri & Desai Amita, GUIDED BY Dr.Tushar Gohil, S. L.P.T.P.M.C-AMRELI 1

PowerPoint Presentation:

2 2 CONTENT:- INTRODUCTION 1.1 .WHAT IS PREFORMULATION 1.2 OBJECTIVE OF PREFORMULATION 1.3 IMPORTANCE OF PREFORMULATION 1.4 GOAL OF PREFORMULATION 1.5 AT WHICH STAGE PREFORMULATION IS REQUIRED 2. ROLE OF PREFORMULATION IN PHARMACEUTICAL PRODCT DEVELOPMENT 3. PROCESS OF PREFORMULATION

PowerPoint Presentation:

3 3 4. VARIOUS PARAMETERS MEASURED IN PREFORMULATION PROCESS. 4.1) EFFECT OF COMPRESION,COMPACTION AND CONSOLIDATION

1.INTRODUCTION::

4 1.INTRODUCTION: 4 1.1 WHAT IS PREFORMULATION: Preformulation testing is the first step in the rational development of dosage forms of a drug substance. It is defined as phase of research and development in which scientist characterize physical, chemical & mechanical properties of new drug molecule in order to develop safe, effective, and stable dosage form. 1.2 OBJECTIVE OF PREFORMULATION: The overall objective of preformulation is to generate information useful to the formulator in developing stable and bioavailable dosage forms which can be mass-produced

PowerPoint Presentation:

5 5 1.3 IMPORTANCE OF PREFORMULATION To form desired quality dosage forms. To achieve high degree of uniformity, physiological availability and therapeutic qualities. To develop an optimum dosage form. For patient compliance. To minimize cost of finished product. To minimize errors in formulation of dosage form. 1.4GOAL OF PREFORMULATION : To establish necessary physicochemical parameter of new drug substance. To determine its kinetic rate profile.

PowerPoint Presentation:

6 6 To determine its physical characteristics. To establish its compatibility with common Excipients. 1.5AT WHAT STAGE PREFORMULATION REQUIRED ? It starts immediately after the synthesis and initial toxicity screening of a new drug. When a newly synthesized drug shows pharmacological evidence that requires further evaluation in man. At the time of finalizing new formulation. When formulation and dosage form changes are required After approval of NDA, production can start .

2. ROLE OF PREFORMULATION IN PHARMACEUTICAL PRODCT DEVELOPMENT: :

7 2. ROLE OF PREFORMULATION IN PHARMACEUTICAL PRODCT DEVELOPMENT: To develop an optimum dosage form thorough understanding of physical and chemical properties as well as pharmacokinetic and biopharmaceutical behaviour of each drug substance being developed is necessary. Drugs substances are administered as chemical entities but almost always are given in some kind of formulation. These may vary from simple solution to very complex drug delivery system. The complexity is not intentional but is determined by properties that are built into dosage form and by resulting composition that is required to achieve qualities. 7

CONTENTS:

8 CONTENTS Definitions Concept of free surface energy Mass-volume relationships Effect of applied forces on powders Role of moisture Granulation

DEFINITIONS :

9 DEFINITIONS COMPACTION : It is defined as ‘Compression & Consolidation’ of a two-phase (particulate solid-gas) system due to the applied force . COMPRESSION : A reduction in the bulk volume of the material as a result of displacement of the gaseous phase. CONSOLIDATION : Increase in the mechanical strength of the material resulting from particle-particle interactions.

PowerPoint Presentation:

10 MECHANISM OF COMPACTION AND COMPRESSION REVERSIBLE PLASTIC DEFORMATION BRITTELE FRACTURE P P(1) P(2) IRREVERSIBLE

PowerPoint Presentation:

11 DIFFERENT STAGES OF POWDER COMPACTION

PowerPoint Presentation:

12 Loose Packing :- Initially, when the powder is filled into the die with the excess of being swept off. Dense Packing :- When upper punch first press down upon the powder bed, the particles rearrange themselves to achieve closer packing. Elastic deformation :- As the upper punch continues to advance upon the powder bed, the rearrangement become more difficult & deformation of particles will undergo elastic deformation, which is a reversible process. Plastic deformation :- As continuous pressure applied, the particle begins to deform irreversibly. Plastic material gets bonded after visco elastic deformation. e.g. MCC undergoes plastic deformation on compression. Compared to MCC Silicified MCC provides increased compactibility , enhanced flow & improved Uniformity. Brittle fracture :- After plastic deformation still pressure is applied in die then a particle fractures into small particles. e.g. Calcium phosphate Plastic deformation is a major factor attributing to the tablet’s mechanical strength or to brittle fraction which produces poor quality GMP act that causes crumbling of tablet during ejection.

PowerPoint Presentation:

13 EVALUTION OF COMPACTION :- Strain index (SI) :- Measures internal strain associated with a powder when compacted. Bonding index (BI) :-Ability of material to bonds. Brittle fracture index (BFI) :- Measures brittleness of material. Higher is the BI index, stronger is the tablet. Higher is the SI index, softer is the tablet. SI BI BFI Erythromycin 2.13 1.9 0.98 MCC 2.20 3.3 0.04 MCC, Erythromycin, etc have high BI and high SI index. So compressibility is moderate.

FREE SURFACE ENERGY:

14 FREE SURFACE ENERGY Atoms or ions located at the surface of any solid particle are exposed to a different distribution of intra & inter molecular bonding forces thal those within the particle. The atoms or ions have some unsatisfied attractive molecular forces extending out some small distance beyond the solid surface.

UNSATISFIED BONDING FORCES AT THE SURFACE OF PARTICLE:

15 UNSATISFIED BONDING FORCES AT THE SURFACE OF PARTICLE COHESION (stay together) : attraction between like particles ADHESION (attraction process between dissimilar molecular species ): approach other type of particles or solid surfaces.

ELECTROSTATIC FORCES:

16 ELECTROSTATIC FORCES Particles when subjected to internal friction there is a particle-particle interaction occur & then charge is developed depends upon the particular material involved. -relatively small -significant because they act over a greater distance than the molecular forces RESISTANCE TO FLOW OF POWDER BY TWO FACTORS 1.ELECTROSTATIC FORCES 2. PRESENCE OF ADSORBED LAYER OF MOISTURE ON THE PARTICLES.

ADSORBED LAYER OF MOISTURE:

17 ADSORBED LAYER OF MOISTURE When the particle approach one another closely enough, however, these films of moisture can form liquid bridges, which hold the particles together by surface tension effects & by negative capillary pessure.

Flow properties:

18 Flow properties Angle of repose: tan θ =2h/D Type of flow <25 Excellent 25-30 Good 30-40 Passable >40 Very poor

Carr’s values: →Below 15-good flow →above 25-poor flow:

19 Carr’s values: →Below 15-good flow →above 25-poor flow Carr’s index(I):

Mass volume relationships::

20 Mass volume relationships : 3 types of air spaces present in the particles a) Open-intra particulate voids b) Closed-intra particulate voids c) Inter particulate voids Volumes : The above voids can define the following volumes. True volume (Vt) - total volume of the solid particles, which excludes all voids. Granular volume (Vg) – cummulative volume occupied by the particles including intra particulate voids. Bulk volume (Vb) – total volume occupied by the entire powder mass under particular packing achieved including all intra as well as inter particulate voids.

Measuring the volume of powders::

21 Measuring the volume of powders: True volume : By 1) X-ray diffraction 2) Helium pycnometer 3) Specific gravity bottle method Granular volume : By 1) Liquid displacement Bulk volume : By 1) Tamping 2) Tapping 3) Vibrating procedures

PowerPoint Presentation:

22 Density (M/v) : True density (Theoretical density) ρ t = M/Vt Granular density ρ g = M/Vg Bulk density ρ b = M/Vb Porosity (E) : The space between the particles in a powder is known to be voids.The volume occupied by such voids is known to be void volume. Void volume=Bulk volume-True volume The porosity or voids,of the powder is defined as ratio of the void volume to the bulk volume of the packing. The relation between compression and porosity is important because porosity determines the rate of disintegration,dissolution and drug absorption. Void volume = Bulk volume-True volume Porosity = Void volume/Bulk volume

EFFECT OF APPLIED FORCES ON GIVEN POWDER: :

23 EFFECT OF APPLIED FORCES ON GIVEN POWDER: DEFORMATION COMPRESSION CONSOLIDATION Deformation : Change in geometry of solid body. Strain – Deformation produced by force. T ensile strain C ompressive strain S hear strain

PowerPoint Presentation:

24 “COMPACTION,COMPRESSION & CONSOLIDATION IN PREFORMULATION” PREPARED BY: Gosai Madhuri & Desai Amita, GUIDED BY Dr.Tushar Gohil, S. L.P.T.P.M.C-AMRELI 24

PowerPoint Presentation:

25 25 Compression Tablet compression machine Effect of compersion and compaction on different factors Consolidation Effect of different factors on consolidation Effect of compression and copsolidation under high load References Topics:

COMPRESSION ::

26 COMPRESSION : When some external forces applied on the powder reduction in the bulk volume of the powder. Rearrangement / Repacking also occur On applying more force Particles undergo certain type of deformation. Two types of deformations 1. Elastic deformation : Removal of upload act like rubber comes to original place, usually all solids undergo elastic deformation. Ex:- Acetyl salicylic acid, MCC. 2. Plastic deformation : They won’t come back to its original volume, completely reduction in the bulk volume. [ When shear strength of particles less than the tensile (breaking) strength of the particles ] Brittle fracture : Shear strength more than the tensile strength.eg.sucrose

PowerPoint Presentation:

27

PowerPoint Presentation:

Tablet Compression Machine Tablets are made by compressing a formulation containing a drug or drugs with excipients on stamping machine called presses. Tablet presses are designed with following basic components : 1) Hopper for holding and feeding granulation 2) Dies that define the size and shape of the tablet. 3) Punches for compressing the granulation within the dies. 4) Cam tracks for guiding the movement of the punches. 5) Feeder a feeding mechanism for moving granulation from hopper into the dies. Rotary Tablet Press

PowerPoint Presentation:

31 EFFECT OF COMPACTION & COMPRESSION ON DIFFERENT FACTORS :- Compaction and Compression force affects surface area, granule density, porosity and hardness and disintegration time of pharmaceutical tablets. Surface area increased to a maximum and then decreased. The initial increase in surface area can be attributed to the formulation of new surface as the primary crystalline material is fragmented while the decrease in specific surface due to cold bonding between the unit particles. Porosity decrease and density increased as a linear function of the logarithm of the compression force. As the compression increase the tablet hardness and fracture resistance also rise.

PowerPoint Presentation:

32 Moisture and Compression:- Moisture decreases particle surface energy & thus decreases adhesion of the tablet to the die wall. In case Moisture increase the tensile strength of the tablet by increasing contact area for bonding of MCC, moisture present within the pores facilitated the flow during the compaction. Excessive moisture produces capillary state of powder aggregation and thus surface tension effects are insignificant to have better compaction and lack of moisture leads to lamination in tablets.

PowerPoint Presentation:

33 ۞ It has also concluded that compaction and compression are important aspects for various compacted dosage forms, like tablets ,pellets. ۞ Force of compaction should be optimized as they affects finally the release of drug from dosage forms . Conclusion

Consolidation : Increase in mechanical strength of the mass:

34 Consolidation : Increase in mechanical strength of the mass Cold welding : When two surfaces of particles approaching together ( distance b/w two layers less than 50nm ) their free surface energies resulting a strong attractive force. Fusion bonding : Under appreciable forces the transmission may result in the generation of frictional heat, there is a local raise in the temperature cause melting of the contact area of the particles and the melt solidifies. Both cold and fusion welding influenced by following factors 1. Chemical nature of the materials. 2. Extent of available surface. 3. The presence of surface contaminants. 4. The inter surface distance.

PowerPoint Presentation:

35 Cubic lattice : The substances processing cubic lattice arrangement for tableted more satisfactorily than those with a rhombohedral lattice. In cubic lattice all the plains are equal length their is no problem easily undergo plastic deformation. Rhombohedral lattice: Rhombohedral structure all the plain alignment not proper.

Surface area ::

36 Surface area : According to HIGUCHI as the increasing the compressional pressure increasing the surface area and increasing the mechanical strength. According to ARMSTRONG at high compressional forces increasing the surface area results in failure of tablet capping occur.

Role of moisture ::

37 Role of moisture : Moisture is necessary for formation of tablet, it can fill the small voids present between the particles. Moisture is also important in wet granulation process. WET GRANULATION / MOIST GRANULATION :

PowerPoint Presentation:

38 Different types of states during moist granulation : Pendular state (powder+binding agent) Funicular state (powder+more binding agent) Capillary state (powder+even more binding agent) Droplete state (powder+even more and more binding agent)

Drying ::

39 Drying : Initial adjust Rate period at 60 0 c at constant rate period surface moisture is removed. First falling rate period : Drying rate will decrease, deeper to surface. Second falling rate period : Heat go inside of the bed vapour will come out of the bed. Residual moisture content is compulsory for granulation.

Properties of granules ::

40 Properties of granules : After granulation step particles shape and size distribution factors in packing and flow. Granules shape and size play important role. Mostly all granules spherical (more regular) we can get less angle of repose and high bulk densities and also have good flow properties & good compression, consolidation.

Effect of compression and consolidation under high loads:

41 Effect of compression and consolidation under high loads Small force- rearrangement occurs High force- deformation usually plastic deformation occurs during tableting. due to development of weak planes capping lamination occurs after decompression. formation of skin: consolidation is more, it is adjacent to die wall formation of skin on the tablet. disadvantages: it will not allow the air to escape from the tablet during compresssion prolonged disintegration & dissolution time

PowerPoint Presentation:

REFERENCES Pharmaceutics by M. E. Aultion, 2nd edition Page 156 – 165. Physical pharmacy by Martin, 3rd edition Page 446. Remington “Pharmaceutical sciences”, 19th edition, vol-2; Page 894, 895, 1447 – 1462, 1620. The theory and Practice of industrial Pharmacy by Lehman, 3rd edition, Page 67, 71, 181. Encyclopedia of Pharmaceutical technology Dekker, vol-11; Page 237 – 258. Ansel’s Pharmaceutical Dosage forms and Drug Delivery Systems, 8th edition, Page 101,190,191,150. Cooper and Gunn’s Tutorial Pharmacy, 6th edition, Pages 174 – 199. (30-32)

PowerPoint Presentation:

Increased output Increased yield Flexible tooling change-over Fast format change-over Low tooling cost Superior tablet quality Superior process control New technology in compression machine with

THANK YOU:

THANK YOU Thank you

authorStream Live Help